tbuckley/cabot-search huggingface dataset:
METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
Authors: Raquel García-Vílchez, Ana M. Añazco-Guenkova, Sabine Dietmann, Judith López, Virginia Morón-Calvente, Silvia D’Ambrosi, Paz Nombela, Kepa Zamacola, Isabel Mendizabal, Saioa García-Longarte, Amaia Zabala-Letona, Ianire Astobiza, Sonia Fernández, Alejandro Paniagua, Borja Miguel-López, Virginie Marchand, Diego Alonso-López, Angelika Merkel, Ignacio García-Tuñón, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Isabel Lacasa-Viscasillas, Miguel Unda, Mikel Azkargorta, Félix Elortza, Laura Bárcena, Monika Gonzalez-Lopez, Ana M. Aransay, Tomás Di Domenico, Manuel A. Sánchez-Martín, Javier De Las Rivas, Sònia Guil, Yuri Motorin, Mark Helm, Pier Paolo Pandolfi, Arkaitz Carracedo, Sandra Blanco
Journal: Molecular Cancer (2023)

Abstract Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N 7 -methylguanosine (m 7 G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m 7 G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m 7 G tRNA methylation in cancer cell translation control and tumour biology.
CGRP‐Loaded Porous Microspheres Protect BMSCs for Alveolar Bone Regeneration in the Periodontitis Microenvironment
Authors: Jiaxin Luo, Hongyan Chen, Guifang Wang, Jiaxuan Lyu, Yulan Liu, Sihan Lin, Mingliang Zhou, Xinquan Jiang
Journal: Advanced Healthcare Materials (2023)

Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3)/Caspase-1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions.
Incorporating Anticoagulant and Antiplatelet Dual Functional Groups into Thermosetting Polymer Chain for Enhancing Antithrombogenicity
Authors: Weizhong Wang, Shaowen Liu, Shan Zhang, Jingjing Zhang, Yuyi Tang, Weijia Zhang
Journal: Advanced Healthcare Materials (2023)

In clinical practice, high-effective antithrombosis remains a challenge for blood-contacting medical devices. Inspired by the enhanced antithrombogenicity of anticoagulant and antiplatelet combination therapy, a strategy is proposed to synthesize dual-pathway antithrombotic polymers by incorporating anticoagulant and antiplatelet dual functional groups into a single thermosetting polymer chain. The synthesized polymer shows increased antithrombogenicity in vitro, with prolonged activated partial thromboplastin time (APTT) and decreased platelet adhesion. Additionally, it downregulates the expression of coagulation- and inflammation-related factors in rabbit plasma after ex vivo arteriovenous shunt assay and maintains patency of small vascular grafts for at least 6 months without thrombosis on the luminal surface after in vivo replacement of rabbit carotid artery. This work provides a new approach to producing novel antithrombotic polymers for blood-contacting medical devices.
NIR light-driven pure organic Janus-like nanoparticles for thermophoresis-enhanced photothermal therapy
Authors: Zhiqiang Ni, Di Zhang, Shijie Zhen, Xiao Liang, Xiangjun Gong, Zujin Zhao, Dan Ding, Guangxue Feng, Ben Zhong Tang
Journal: Biomaterials (2023)
Biomimetic Adhesive Micropatterned Hydrogel Patches for Drug Release
Authors: Katia R. Amaral, A. Sofia Silva, Lúcia F. Santos, Edgar J. Castanheira, Maria C. Mendes, Dora C.S. Costa, João M. M. Rodrigues, Joana Marto, João F. Mano
Journal: Advanced Healthcare Materials (2023)

The optimized physical adhesion between bees' leg hairs and pollen grains-whereby the latter's diameter aligns with the spacing between the hairs-has previously inspired the development of a biomimetic drug dressing. Combining this optimized process with the improved natural mussels' adhesion in wet environments in a dual biomimetic process, it is herein proposed the fabrication of a natural-derived micropatterned hydrogel patch of methacrylated laminarin (LAM-MET), with enriched drug content and improved adhesiveness, suitable for applications like wound healing. Enhanced adhesion is accomplished by modifying LAM-MET with hydroxypyridinone groups, following the patch microfabrication by soft lithography and UV/vis-irradiation, resulting in a membrane with micropillars with a high aspect ratio. Following the biomimetics rational, a drug patch is engineered by combining the microfabricated dressing with drug particles milled to fit the spaces between pillars. Controlled drug release is achieved, together with inherent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, and enhanced biocompatibility using the bare micropatterned patches. This new class of biomimetic dressings overcomes the challenges of current patches, like poor mechanical properties and biocompatibility, limited adhesiveness and drug dosage, and lack of prolonged antimicrobial activity, opening new insights for the development of high drug-loaded dressings with improved patient compliance.
Targeted Delivery of the Pan‐Inflammasome Inhibitor MM01 as an Alternative Approach to Acute Lung Injury Therapy
Authors: Alba García‐Fernández, Mónica Sancho, Eva Garrido, Viviana Bisbal, Félix Sancenón, Ramón Martínez‐Máñez, Mar Orzáez
Journal: Advanced Healthcare Materials (2023)

Acute lung injury (ALI) is a severe pulmonary disorder responsible for high percentage of mortality and morbidity in intensive care unit patients. Current treatments are ineffective, so the development of efficient and specific therapies is an unmet medical need. The activation of NLPR3 inflammasome during ALI produces the release of proinflammatory factors and pyroptosis, a proinflammatory form of cell death that contributes to lung damage spreading. Herein, it is demonstrated that modulating inflammasome activation through inhibition of ASC oligomerization by the recently described MM01 compound can be an alternative pharmacotherapy against ALI. Besides, the added efficacy of using a drug delivery nanosystem designed to target the inflamed lungs is determined. The MM01 drug is incorporated into mesoporous silica nanoparticles capped with a peptide (TNFR-MM01-MSNs) to target tumor necrosis factor receptor-1 (TNFR-1) to proinflammatory macrophages. The prepared nanoparticles can deliver the cargo in a controlled manner after the preferential uptake by proinflammatory macrophages and exhibit anti-inflammatory activity. Finally, the therapeutic effect of MM01 free or nanoparticulated to inhibit inflammatory response and lung injury is successfully demonstrated in lipopolysaccharide-mouse model of ALI. The results suggest the potential of pan-inflammasome inhibitors as candidates for ALI therapy and the use of nanoparticles for targeted lung delivery.
Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype
Authors: Antoine Fayand, Margaux Cescato, Laurent Le Corre, Alexandre Terré, Margaux Wacheux, Yixiang Y.J. Zhu, Armelle Melet, Thomas R.J. Moreau, Bahram Bodaghi, Fabrice Bonnet, Didier Bronnimann, Laurence Cuisset, Raquel Faria, Gilles Grateau, Pascal Pillet, Catharina M. Mulders-Manders, Benedicte Neven, Pierre Quartier, Olivier Richer, Léa Savey, Marie-Elise Truchetet, Bénédicte F. Py, Guilaine Boursier, Jean-Philippe Herbeuval, Sophie Georgin-Lavialle, Mathieu P. Rodero
Journal: Journal of Allergy and Clinical Immunology (2023)
A self-unfolding proximity enabling device for oral delivery of macromolecules
Authors: Mahdi Ghavami, Jesper Pedersen, Rolf Bech Kjeldsen, Aage Kristian Olsen Alstrup, Zhongyang Zhang, Vasiliki Koulianou, Johan Palmfeldt, Thomas Vorup-Jensen, Lasse Højlund Eklund Thamdrup, Anja Boisen
Journal: Journal of Controlled Release (2023)

Oral delivery of macromolecules remains highly challenging due to their rapid degradation in the gastrointestinal tract and poor absorption across the tight junctions of the epithelium. In the last decade, researchers have investigated several medical devices to overcome these challenges using various approaches, some of which involve piercing through the intestine using micro and macro needles. We have developed a new generation of medical devices called self-unfolding proximity enabling devices, which makes it possible to orally deliver macromolecules without perforating the intestine. These devices protect macromolecules from the harsh conditions in the stomach and release their active pharmaceutical ingredients in the vicinity of the intestinal epithelium. One device version is a self-unfolding foil that we have used to deliver insulin and nisin to rats and pigs respectively. In our study, this device has shown a great potential for delivering peptides, with a significant increase in the absorption of solid dosage of insulin by ∼12 times and nisin by ∼4 times in rats and pigs, respectively. With the ability to load solid dosage forms, our devices can facilitate enhanced absorption of minimally invasive oral macromolecule formulations.
Patients with <scp>naproxen‐induced</scp> liver injury display T‐cell memory responses toward an oxidative (S)‐<scp>O‐desmethyl</scp> naproxen metabolite but not the acyl glucuronide
Authors: Paul Thomson, Nik Fragkas, Laila M. Kafu, Guruprasad P. Aithal, M. Isabel Lucena, Luigi Terracciano, Xiaoli Meng, Munir Pirmohamed, Dominique Brees, Gerd A. Kullak‐Ublick, Alex Odermatt, Thomas Hammond, Michael Kammüller, Dean J. Naisbitt
Journal: Allergy (2023)

Abstract Background Exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug‐induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g., acyl glucuronides, AG) and resulting T‐cell activation is hypothesized as causal for this adverse event. However, conclusive evidence supporting this is lacking. Methods In this work, we identify CD4 + and CD8 + T‐cell hepatic infiltration in a biopsy from an IBU DILI patient. Lymphocyte transformation test and IFN‐γ ELIspot, conducted on peripheral blood mononuclear cells (PBMCs) of patients with NAP‐DILI, were used to explore drug‐specific T‐cell activation. T‐cell clones (TCC) were generated and tested for drug specificity, phenotype/function, and pathways of T‐cell activation. Cells were exposed to NAP, its oxidative metabolite 6‐O‐desmethyl NAP (DM‐NAP), its AG or synthesized NAP‐AG human‐serum albumin adducts (NAP‐AG adduct). Results CD4 + and CD8 + T‐cells from patients expressing a range of different Vβ receptors were stimulated to proliferate and secrete IFN‐γ and IL‐22 when exposed to DM‐NAP, but not NAP, NAP‐AG or the NAP‐AG adduct. Activation of the CD4 + TCC was HLA‐DQ‐restricted and dependent on antigen presenting cells (APC); most TCC were activated with DM‐NAP‐pulsed APC, while fixation of APC blocked the T‐cell response. Cross‐reactivity was not observed with structurally‐related drugs. Conclusion Our results confirm hepatic T‐cell infiltrations in NSAID‐induced DILI, and show a T‐cell memory response toward DM‐NAP indicating an immune‐mediated basis for the adverse event. Whilst bioactivation at the carboxylate group is widely hypothesized to be pathogenic for NSAID associated DILI, we found no evidence of this with NAP.
Performance of <scp>IPSS‐M</scp> in patients with myelodysplastic syndrome after hypomethylating agent failure
Authors: Samuel Urrutia, Kelly S. Chien, Ziyi Li, Alex Bataller, Emmanuel Almanza, Koji Sasaki, Guillermo Montalban‐Bravo, Nicholas J. Short, Elias Jabbour, Tapan M. Kadia, Farhad Ravandi, Gautam Borthakur, Yesid Alvarado, Naval Daver, Rashmi Kanagal‐Shamanna, Carlos Bueso‐Ramos, Sherry A. Pierce, Hagop Kantarjian, Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2023)

Evaluation of IPSS-M and exploratory prognostic model for MDS at the time of HMA failure.
Virtual cardiovascular magnetic resonance training proves feasible and effective: survey data from international participants of the CMR Academy Berlin, Germany
Authors: Djawid Hashemi, Patrick Doeblin, Karl Jakob Weiss, Matthias Schneider-Reigbert, Rebecca Elisabeth Beyer, Corinna Else, Alessandro Faragli, Christian Stehning, Philipp Stawowy, Steffen E Petersen, Chiara Bucciarelli-Ducci, Allison G Hays, Norbert Frey, Holger Thiele, Andreas Portmann, Eckart Fleck, Sebastian Kelle
Journal:  (2023)

Abstract Aims This study aims to evaluate the success of the cardiovascular magnetic resonance (CMR) imaging Academy Berlin’s transition from in-person to online CMR imaging training during the global pandemic 2020 and to gather recommendations for future courses. Methods and results We conducted an online survey targeting CMR course participants from both the pre-pandemic, in-person era and the pandemic, online era of the CMR Academy Berlin. The survey primarily used Likert-type questions to assess participants’ experiences and preferences. A total of 61 out of 158 invited participants (38.61%) completed the survey, with 31 (50.82%) being in-person alumni and 30 (49.18%) being online alumni. Both in-person [83.87% (26/31)] and online [83.33% (25/30)] participants rated the course as either ‘very good’ or ‘excellent’, and both groups found the course either ‘extremely helpful’ or ‘very helpful’. However, a higher percentage of in-person participants [96.77% (30/31)] felt comfortable asking questions compared to online participants [83.33% (25/30); P = 0.025]. The majority in both groups preferred a written exam [total: 75.41% (46/61); in-person alumni: 77.42% (24/31); online alumni 73.33% (22/30)]. In terms of course format preferences, in-person courses were preferred by both in-person alumni [38.71% (12/31)] and online alumni [60% (18/30)], almost as much as a hybrid format combining in-person and online elements [in-person alumni: 41.94% (13/31), online alumni: 30% (9/30)]. Conclusion The transition from in-person to online CMR training at the CMR Academy Berlin was successful in maintaining overall satisfaction. However, there is room for improvement in terms of increased interaction, particularly for online participants. Future CMR- and potentially also cardiac computer tomography-courses should consider adopting a hybrid format to accommodate participants’ preferences and enhance their learning experience, especially to gain level II competency, whereas level I virtual only might be sufficient.
Management of temporary mechanical circulatory support devices in cath-lab and cardiac intensive care unit
Authors: Federico Fortuni, Filippo Zilio, Gianmarco Iannopollo, Giuseppe Ciliberti, Paolo Trambaiolo, Laura Ceriello, Francesca Musella, Pietro Scicchitano, Stefano Albani, Stefania Angela Di Fusco, Michele Massimo Gulizia, Domenico Gabrielli, Fabrizio Oliva, Furio Colivicchi
Journal:  (2023)

Abstract Different temporary mechanical circulatory support (tMCS) devices are available and can be used to maintain end-organ perfusion while reducing cardiac work and myocardial oxygen demand. tMCS can provide support to the right ventricle, left ventricle, or both, and its use can be considered in emergency situations such as cardiogenic shock or in elective procedures such as high-risk percutaneous coronary intervention to prevent haemodynamic deterioration. Invasive and, most importantly, non-invasive haemodynamic parameters should be taken into account when choosing the type of tMCS device and its initiation and weaning timing, determining the need for a device upgrade, and screening for complications. In this context, ultrasound tools, specifically echocardiography, can provide important data. This review aims to provide a description of the different tMCS devices, the invasive and non-invasive tools and parameters to guide their management, and their advantages and drawbacks.
Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience
Authors: Se In Jeong, Woochul Kim, Hyeong Won Yu, June Young Choi, Chang Ho Ahn, Jae Hoon Moon, Sang Il Choi, Wonjae Cha, Woo-Jin Jeong, So Yeon Park, Hee Young Na
Journal: Endocrine Pathology (2023)
The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy
Authors: Wenyan Xu, Lingran Du, Lina Yu, Huiyu Cen, Fangyu Lin, Siran Wang, Zhixiong Ruan, Zhongxiao Lin, Xin Zhang, Na Zhou, Jishuo Chang, Xiyong Yu, Lingmin Zhang, Lu Liang
Journal: MedComm (2023)

Gene therapy has emerged as a potential approach for lung cancer therapy. However, the application of gene therapy is still limited by their properties, such as low specificity to the cancer cells, negatively charged groups, short systemic circulation time, and rapid degradation by nucleases. The progression of lung adenocarcinoma (LUAD) can be promoted through the methylation process of miR-148a-3p promoter, as confirmed by our previous research. In the current study, we are the first to design a mirrored Arg-Gly-Asp (RGD)-modified cationic peptide (RD24) as a microRNA (miRNA) vehicle, which enabled to pack the miRNA (miR-148a-3p) efficiently and generate RD24/miR-148a-3p nanoparticles (RPRIN) by self-assembling. RPRIN exhibited a high transfection efficiency in lung cancer cells via the conjugation between RGD and integrins on the surface of lung cancer cells. Furthermore, RD24 showed matrix metallopeptidase 2 (MMP2) responsiveness, which improved lung cancer cell inhibition induced by the miRNA intracellularly. In addition, RPRIN exhibits several advantages, such as prolonged circulation duration, reduced toxicity, and immune escape. Experiments conducted both in vitro and in vivo revealed that RPRIN effectively suppressed the growth and progression of lung cancer. Thus, the mirrored RGD-modified cationic peptide showed great potential in transducing miRNA for lung cancer therapy.
The shaky foundations of large language models and foundation models for electronic health records
Authors: Michael Wornow, Yizhe Xu, Rahul Thapa, Birju Patel, Ethan Steinberg, Scott Fleming, Michael A. Pfeffer, Jason Fries, Nigam H. Shah
Journal: npj Digital Medicine (2023)

The success of foundation models such as ChatGPT and AlphaFold has spurred significant interest in building similar models for electronic medical records (EMRs) to improve patient care and hospital operations. However, recent hype has obscured critical gaps in our understanding of these models' capabilities. In this narrative review, we examine 84 foundation models trained on non-imaging EMR data (i.e., clinical text and/or structured data) and create a taxonomy delineating their architectures, training data, and potential use cases. We find that most models are trained on small, narrowly-scoped clinical datasets (e.g., MIMIC-III) or broad, public biomedical corpora (e.g., PubMed) and are evaluated on tasks that do not provide meaningful insights on their usefulness to health systems. Considering these findings, we propose an improved evaluation framework for measuring the benefits of clinical foundation models that is more closely grounded to metrics that matter in healthcare.
Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies
Authors: Shan Muhammad, Tao Fan, Yang Hai, Yibo Gao, Jie He
Journal: Molecular Cancer (2023)

Abstract Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function and expression in the tumor microenvironment make them attractive targets for immunotherapy, leading to the development of IL-2/IL-2R-targeted therapeutic strategies. However, the dynamic interplay between IL-2/IL-2R and various immune cells and their dual roles in promoting immune activation and tolerance presents a complex landscape for clinical exploitation. This review discusses the pivotal roles of IL-2 and IL-2R in tumorigenesis, shedding light on their potential as diagnostic and prognostic markers and their therapeutic manipulation in cancer. It underlines the necessity to balance the anti-tumor activity with regulatory T-cell expansion and evaluates strategies such as dose optimization and selective targeting for enhanced therapeutic effectiveness. The article explores recent advancements in the field, including developing genetically engineered IL-2 variants, combining IL-2/IL-2R-targeted therapies with other cancer treatments, and the potential benefits of a multidimensional approach integrating molecular profiling, immunological analyses, and clinical data. The review concludes that a deeper understanding of IL-2/IL-2R interactions within the tumor microenvironment is crucial for realizing the full potential of IL-2-based therapies, heralding the promise of improved outcomes for cancer patients.